Diagnosis and Management of Fetal Disorders

By Boris M. Petrikovsky and Harris L. Cohen

Diagnosis and Management of Fetal Disorders reviews key points in obstetrics/maternal fetal medicine imagery analysis of the pregnant uterus and its contents. Specifically, chapters cover ultrasound of different fetal organs, physiological systems and diseases. The authors also provide radiological correlation to help the obstetrician, pediatrician, radiologist, and other specialists know the basics and some more advanced concepts that will allow diagnosis of fetal abnormality, and what those findings mean to the patient and their families vis-a-vis the fetus in their pregnancy. It is ,therefore, a handbook that helps medical residents and professionals to assess cases in real-time or to review a given clinical problem.

Key Features
- 13 structured chapters covering key topics related to the ultrasound of different fetal organs, physiological systems and diseases
- Evidence-based presentation through detailed images
- Portability and practical information on general and differential diagnostics to consider in fetal and uterine examinations.
- Useful information for medical and genetic counseling for mothers and couples
- References for advanced readers

The book is intended for a broad readership in medicine including medical students, specialty trainees and attending physicians in obstetrics, pediatrics, radiology, and subspecialty trainees in maternal fetal medicine, neonatology, ultrasound diagnostics. Medical professionals in allied fields including sonography, family practice, and genetic counseling will also benefit from the information presented in the book.

• Language: English
• Publisher: Bentham Science Publishers
• Release date: Jul 16, 2009
• ISBN: 9789815079630

Book preview

Abnormalities of the Central Nervous System

Boris M. Petrikovsky, Harris L. Cohen

Introduction

Anomalies of the central nervous system include birth defects of the brain and spinal cord. These abnormalities may be caused by a variety of factors including genetics, medications, toxins, and infectious agents, among others. Central nervous system abnormalities may be divided into three groups: incompatible with life (e.g., anencephaly), requiring in-utero surgery in some cases (e.g., spina bifidum), or post-delivery follow-up and/or treatment (e.g., ventriculomegaly).

Agenesis Of The Corpus Callosum

Definition: The corpus callosum is the largest of the medial interhemispheric commissures connecting the right and left halves of the brain. In agenesis of the corpus callosum (ACC) the connecting neurofibers of the commissure fail to develop.

Prevalence: 3.5 per 1000 live births [1].

Major Principles of Diagnosis: At times, the sonographic diagnosis of ACC may be difficult: 10 to 15% of ACC cases may be missed including in patients who underwent more than one ultrasound examination during their pregnancy. Ultrasound signs of agenesis of the corpus callosum include wide separation of the frontal horns of the lateral ventricles and a high riding third ventricle because the corpus callosum is no longer present to prevent its upward positioning. Lateral ventricles may be teardrop shaped (colpocephaly) with only the posterior portion full or dilated. Image findings of concern for ACC include difficulty in imaging a cavum septum pellucidum and mild ventriculomegaly including the aforementioned colpocephaly with its enlargement of the occipital horns of the lateral ventricles.

At times one may see an associated midline cyst and /or lipoma [2]. The cavum septum pellucidum (CSP) which is absent in cases of ACC would normally appear as two parallel lines separated by cerebrospinal fluid (CSF). A cavum may be seen between the frontal horn as early as 14 weeks gestational age in the axial (BPD) plane. In complete agenesis of the corpus callosum, a cavum is not seen. It

is absent in a complete ACC although it may be seen in cases of partial ACC. If a septum pellucidum cannot be found and there is dilation of the occipital horns, differential diagnostic considerations should include lobar (but not alobar holoprosencephaly with its single ventricle) and agenesis of the corpus callosum. Nonvisualization or an abnormal appearing CSP and/or ventriculomegaly are the most common indications for MRI of the fetal brain. MRI can detect most callosal dysmorphology by 22 weeks gestation. This may include complete or partial ACC and some associated abnormalities such as septo-optic dysplasia, neuromigrational abnormalities and brainstem kinking (pontomesencephalic dysmorphology). Complete brain anatomy evaluation may help note any concern for a syndromic abnormality. Such information helps in parental counselling regarding the fetal/perinatal prognosis. MRI timing should balance the need for earlier diagnosis with the greater ease of anatomical imaging of the brain in later 2nd and 3rd trimesters [3].

Early Diagnosis: Corpus callosum development is not complete until at least 18-20 weeks gestation, A first trimester diagnosis is therefore not feasible.

MRI Diagnosis: MRI can image a normal versus an abnormal corpus callosum after 22 weeks and in many cases between 20-22 weeks [4] (Fig. 1). Examinations performed after 30 weeks can evaluate the brain's gyral pattern to rule out any associated lissencephaly.

Prenatal Management: Prenatal management should include a search for any associated abnormality, Karyotyping, microarray analysis, counseling by a pediatric neurologist or neurosurgeon, and serial ultrasounds can help note if there is progressive ventriculomegaly.

Prognosis: At least 60% of children with isolated ACC may have mild behavioral problems. Agenesis of the corpus callosum (whether partial or complete) seems to have no bearing on the prognosis. Patients with agenesis of the corpus callosum may have difficulties with language (expressive) and/or social skills. Familial recurrence of ACC depends on its etiology and ranges between 2 to 4% [5-9].

Fig. (1))

Agenesis of Corpus Callosum. MRI.

Anencephaly and Acrania

Definition: Anencephaly is an anomaly in which the cerebral hemisphere and skull are absent. Acrania, or exencephaly, is characterized by the absence of the skull, bones, or cranium. Despite this, substantial brain tissue may be present.

Prevalence: Anencephaly is the commonest neural tube defect (NTD) occurring in 1/1000 pregnancies [10]. Anencephaly occurs when there is failed closure of the rostral neuropore. This occurs during the first 28 days following conception [11].

Acrania develops early in the fourth week of gestation. The cranial bones do not develop, and the brain is exposed to amniotic fluid [10].

Major Principles of Diagnosis: Anencephaly is diagnosed when the upper portion of the cranial vault is not visualized. Despite some sources suggesting a normal facial appearance, the orbits without the calvarium look like those of a frog (frog eyes) or Mickey Mouse ears linked to the fetal face (Fig. 2).

Fig. (2a))

Anencephaly. Ultrasound.

Early Presentation: Cranial calcification occurs at 11-12 weeks of pregnancy. A murky appearance of amniotic fluid in the first trimester of pregnancy is concerning for anencephaly.

Genetics: Anencephaly results from the failure of closure of the rostral neuropore within the first 28 days following conception [11]. Acrania originates at the beginning of the fourth week. The bony tissue over the brain fails to develop, leaving the brain exposed to amniotic fluid [10]. Neural tube defects, including anencephaly and acrania, have multifactorial etiologies. Anencephaly has also been associated with amniotic band syndrome, chromosomal abnormalities (trisomy 18, ring chromosome 13), prenatal folic acid antagonist exposure, maternal diabetes, and hyperthermia [10-12]. Syndromes in which anencephaly has been reported include Meckel-Gruber, hydrolethalus, and acrocallosal disorders, among others [13]. Anencephaly is frequently associated with other malformations, including facial clefts, ear and nose anomalies, congenital heart, renal and gastrointestinal defects, and micropenis. Karyotyping is not needed in cases of isolated anencephaly. Amniocentesis should be offered when other anomalies are noted [10]. Recurrence risks for future pregnancies is 2% to 5%. Folate given as a preconceptual supplement may reduce the risk of reoccurrence by 70%

Prenatal Management: Anencephaly and acrania are uniformly lethal. Pregnancy termination should be offered in case of either anomaly. If the patient chooses to continue the pregnancy, nonaggressive obstetric management is indicated.

Neonatal Outcome: Essentially all neonates die within the first postnatal week. If intubated, it is likely that a neonate can be kept alive for longer. This fact has important implications for harvesting organs for transplantation [10].

Fig. (2b))

Anencephaly. Ultrasound (3D image).

Brain Cysts

Intracranial cysts may be extra-axial (arachnoid), intraparenchymal (periventricular pseudocyst) or intraventricular (choroid plexus cysts).

Arachnoid cyst

Definition: Arachnoid cysts are unilocular and avascular cysts which do not communicate with the ventricles (Figs. 3 and 4). They are often found between the hemispheres in the brain midline. One in ten are found in the posterior fossa typically posterior to the vermis. They can be mistaken for abnormalities of the cisterna magna. Their asymmetry and often off midline position in the posterior fossa solidify the diagnosis of a subtentorial arachnoid cyst rather than a Dandy-Walker cyst. Arachnoid cysts are typically detected after 20 weeks of gestation.

Fig. (3))

Arachnoid Cyst. Ultrasound.

Fig. (4))

Arachnoid Cyst. MRI.

Genetics and Perinatal Management: Arachnoid cysts are associated with other CNS anomalies in over 50% of cases [14]. The most common CNS anomalies are absent septum pellucidum and agenesis of the corpus callosum [15, 16]. There are rare associations with chromosomal defects, mainly trisomy18 or trisomy 12. Ultrasound scans every 4 weeks help monitor the size of the cyst and possible compression resulting in ventriculomegaly. Fetal brain MRI may be useful if ultrasound suggests the presence of other brain abnormalities. The presence of an arachnoid cyst is not an indication for cesarean section as long as the head circumference is less than 40cm.

Neonatal Management and Prognosis: Isolated small cysts are associated with normal neurodevelopment. Large and compressing cysts, when present, may require surgery to prevent long-term sequelae, including seizures, headache, motor deficit, or developmental delay. Only 2% of affected individuals are symptomatic [17]. The recurrence rate is very low. Familial cases of fetal arachnoid cyst have been reported [14].

Cavum Septi Pellucidi and Vergae and Their Abnormalities

Definition: The cavum septi pellucidi (CSP) is a fluid-filled cavity noted in the midline of the brain between the frontal horns. This cavity will normally close when its lateral borders, the two septa, typically come together near term [18]. These septa are translucent leaflets extending from the corpus callosum to the superior aspect of each fornix. The fluid-filled CSP may extend posteriorly as the cavum vergae. It is noted in the midline of the sagittal view below the corpus callosum [19]. The cavum vergae is a posterior extension of the CSP.

Prevalence: 1.4 per 1,000 ultrasound examinations [20].

Major Principles of Diagnosis: An inability to image the cavum septi pellucidi is not uncommon before 20 weeks. In such cases, the patient should be reevaluated on a follow-up ultrasound [20]. Cavum septi pellucidi is best detected on a coronal view of the fetal brain between the frontal horns of the lateral ventricles or a midline sagittal view. The size of the cavum septi pellucidi whether determined by width or AP diameter differs significantly between the second and third trimesters. Like the BPD, CSP measurements correlate with gestational age. The cavum septi pellucidi closes with greater gestational age. It can be found in 90% of premature but only 60% of full-term infants. A cavum vergae can be seen in any fetus less than 28 weeks’ gestation. Cavum vergae closure is also more common as gestational age increases.

Early Presentation: Since septi pellucidi begins to develop at 10-12 weeks gestation, their visualization is not expected in the first trimester.

Prenatal Management:

1. Search for associated anomalies

2. Karyotyping, microarray analysis

Prognosis: The discovery of an enlarged cavum septi pellucidi or cavum vergae in the absence of any other anomaly is of unclear clinical significance [20]. Enlargement of a cavum septi pellucidi has been reported in fetuses with 22q11 deletion syndrome, arthrogryposis, polycystic kidneys, cystic hygroma, short stature, hydrocephalus, periventricular calcification, myotonic dystrophy, volvulus, and congenital heart disease [20-24]. The presence of a large cavum septi pellucidi was significantly higher in a group of patients with schizophrenia spectrum disorders compared to controls (odds ratio, 1.59) [23]. Of note, is the fact that schizophrenia has also been associated with 22q11 deletion syndrome [23]. Absence of the septum pellucidum (ASP) may be associated with De Morsier syndrome, which may have hypothalamic deficiency, and/or optic nerve hypoplasia (Figs. 5 and 6). Some of these patients may have schizencephaly. Absence of septi pellucidi may be simulated by their fenestration from the pressure on them over time in cases of hydrocephalus.

Fig. (5))

Absent Septi Pellucidi. Ultrasound.

Cephalocele

Definition: Cephalocele is a herniation of cranial contents through a skull defect. When the cephalocele contains brain tissue, it is called an encephalocele. If it contains cerebrospinal fluid only, it is called a meningocele [25]. Cephaloceles may be frontal, basal, or occipital. They may be transethmoidal, sphenoethmoidal, sphenomaxillary, spheno-orbital, intrasphenoidal midline transtemporal or transsphenoidal [26]. Atretic encephaloceles are skin-covered sub-scalp lesions typically in the parietal or occipital regions and often associated with other intracranial abnormalities. An occipital encephalocele protrudes through the occipital bone or through the foramen magnum. It is the most common type of encephalocele in the Western hemisphere [26]. Frontoethmoidal encephaloceles are common among Asians [27].

Fig. (6))

Absent Septi Pellucidi. MRI.

Prevalence: 0 .8 per 10.000 births [25].

Major Principles of Diagnosis: Cephalocele is a cystic or predominantly solid mass that extends through a defect in the calvarium (Fig. 7). The defect in the skull may sometimes be visible (Fig. 8). The head circumference and biparietal diameter may be significantly smaller than expected [28].

Early Diagnosis: 80% of posterior encephaloceles are detected during the first trimester of pregnancy [29].

Genetics and Prenatal Management: Most cases of encephalocele are sporadic. If a posterior encephalocele is part of an autosomal recessive disorder, the recurrence risk is 25% [28]. An amniocentesis or chorionic villus sampling with chromosomal microarray analysis (CMA) should be offered in fetuses noted to have a cephalocele. If there are additional anomalies or a family history of a specific condition, exome sequencing may be useful since CMA does not detect single gene disorders [28]. The most common genetic syndromes associated with a cephalocele include: Apert, Meckel-Gruber, Walker, Roberts, Fried-Meckel, and Voss-Cherstvoy. Serial sonographic assessments with MRI for selected cases as well as fetal echocardiography are indicated. Cesarean sections are indicated for large lesions to minimize brain trauma. There is no fetal intervention for this condition. Delivery should take place in a tertiary center that has facilities to manage the baby postnatally [26].

Fig. (7))

Encephalocele. Ultrasound. (Arrows point to occipital bone defect).

Fig. (8))

Occipital Encephalocele. MRI.

Prognosis: The prognosis for neonates with encephalocele depends on the location, size, content of the lesion, and presence of associated intracranial and extracranial malformations [30]. Postnatally, encephaloceles require surgery. In cases of frontal lesions, extensive craniofacial surgery may be required. The long-term outcome is dependent on the amount of brain tissue that has herniated and the presence of microcephaly. Hydrocephalus develops in a significant proportion of affected cases [26]. Many children with encephalocele do not reach their developmental milestones. Affected patients may have or develop ataxia, visual impairment, growth restriction, intellectual disability, and /or seizures [30].

Choroid Plexus Cyst

Definition: A choroid plexus cyst is a cystic structure located in the choroid plexus of the cerebral ventricles. Choroid plexus cysts are not true cysts, but fluid filled spaces of the choroid plexus (Fig. 9).

Fig. (9))

Choroid Plexus Cysts. Ultrasound.

Prevalence: 2 in 100 pregnancies [31].

Genetics: Noting the presence of choroid plexus cysts is important because of their association with aneuploidy, most particularly trisomy 18. They are no longer thought to be associated with trisomy 21. Choroid plexus cysts if present are usually detected between 14 and 22 weeks of pregnancy and are typically less than 10mm. They are commonly unilateral but can be bilateral. Chromosomal abnormalities, specifically trisomy 18, should be ruled out particularly if the choroid plexus cyst is larger than 1cm or if multiple, bilateral, or irregularly shaped cysts are noted. The risk of an associated trisomy is 2.05% [32-34].

Prenatal Management and Prognosis: Once a choroid plexus cyst is detected a detailed ultrasound examination should be performed with special attention to aneuploidy markers [35]. Noninvasive prenatal testing should be offered if choroid plexus cysts and other associated anomalies are found [36]. In the absence of other structural and chromosomal abnormalities, prognosis is excellent [37].

Disorders of the Posterior Fossa: Dandy-Walker Continuum, Persistent Blake’s Pouch Cyst, and Mega Cisterna Magna

Definition: Dandy-Walker continuum is a spectrum of findings in the posterior fossa including the classic Dandy-Walker malformation, persistent Blake’s pouch, and mega cisterna magna. In a persistent Blake’s pouch, the vermis of the cerebellum is fully formed, but neither the pouch nor the foramina of Luschka fenestrate preventing its normal decompression and the transit of CSF beyond the 4th ventricles. In abnormalities of the Dandy-Walker continuum, vermian hypoplasia of variable degrees is often detected. In a mega cisterna magna, the vermis of the cerebellum is fully formed, but the normal fenestration of